EGF_CA

Calcium-binding EGF-like domain		 EGF_CA
SMART accession number:SM00179
Description:
Interpro abstract (IPR001881):

A sequence of about forty amino-acid residues found in epidermal growth factor (EGF) has been shown [(PUBMED:2288911), (PUBMED:6334307), (PUBMED:3534958), (PUBMED:6607417), (PUBMED:3282918), ] to be present in a large number of membrane-bound and extracellular, mostly animal, proteins. Many of these proteins require calcium for their biological function and a calcium-binding site has been found at the N terminus of some EGF-like domains [(PUBMED:1527084)]. Calcium-binding may be crucial for numerous protein-protein interactions.

For human coagulation factor IX it has been shown [(PUBMED:7606779)] that the calcium-ligands form a pentagonal bipyramid. The first, third and fourth conserved negatively charged or polar residues are side chain ligands. The latter is possibly hydroxylated (see aspartic acid and asparagine hydroxylation site) [(PUBMED:1527084)]. A conserved aromatic residue, as well as the second conserved negative residue, are thought to be involved in stabilising the calcium-binding site.

As in non-calcium binding EGF-like domains, there are six conserved cysteines and the structure of both types is very similar as calcium-binding induces only strictly local structural changes [(PUBMED:1527084)].


                             +------------------+        +---------+
                             |                  |        |         |
               nxnnC-x(3,14)-C-x(3,7)-CxxbxxxxaxC-x(1,6)-C-x(8,13)-Cx
                   |                  | 
                   +------------------+
'n': negatively charged or polar residue [DEQN]
'b': possibly beta-hydroxylated residue [DN]
'a': aromatic amino acid
'C': cysteine, involved in disulphide bond
'x': any amino acid.
GO function:calcium ion binding (GO:0005509)
Family alignment:
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There are 28035 EGF_CA domains in 6091 proteins in SMART's nrdb database.

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